Method of treating ceramic surfaces

ABSTRACT

The invention relates to methods for treating ceramic surfaces to decrease their wettability by aqueous solutions. One method involves polishing the ceramic surface until wettability is decreased, and a second method involves a silane heat treatment. Both methods can be used to produce ceramic supports for IEF and electrophoresis gels, as well as microarray plates.

[0001] This application claims benefit of the filing date of U.S.Provisional Application Serial No. 60/111,887, filed Dec. 11, 1998, theentire contents of which is hereby incorporated by reference.

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] The invention relates to methods for modifying the surfaces ofceramic materials in order to alter the interfacial energy of thesesurfaces with liquids, thereby rendering the ceramic materials moresuitable for use as sample holders for electrophoresis and/orisoelectric focusing. The invention also relates to devices made withceramics having such modified surfaces, and in particular relates toceramic vessels used in electrophoresis.

[0004] 2. Description of Related Art

[0005] The ability of a liquid phase to wet a solid phase is related tothe difference between the work of adhesion (i.e., the work required toseparate the immiscible liquid and solid phases) and the work ofcohesion (i.e., the work required to separate the liquid from itself).If the work of adhesion is sufficiently greater than the work ofcohesion, the liquid-solid system will have a positive spreadingcoefficient, and wetting of the solid by the liquid will spontaneouslyoccur. If the work of cohesion of the liquid is greater than the work ofadhesion, the spreading coefficient will be negative, and wetting willnot spontaneously occur (because additional work will be required toovercome the attraction of the liquid for itself and make it spreadacross the solid surface). The determination of works of adhesion, worksof cohesion, and spreading coefficient are related to the surfacetension, and to the closely related concept of contact angle.

[0006] Surface tension can be thought of as the change in Gibbs freeenergy per unit change in the surface area. Contact angle is measured ata gas, solid, liquid interface of a sessile or pendant drop of liquid ona solid surface, typically by an optical comparator. A larger contactangle, θ indicates a decreased wetting by the liquid of the solid. Acontact angle of 0 indicates that the liquid completely wets the solid.See Hiemenz, Principles of Colloid and Surface Chemistry, Marcel Dekker,1977, pp. 209-251, the entire contents of which is hereby incorporatedby reference.

[0007] Isoelectric focusing (IEF) is a technique widely used to separateproteins according to their different isoelectric points. A samplecontaining proteins to be separated is placed on a gel, often a singlelane gel or gel strip having a pH gradient (such gels are typicallyobtained by electrophorescing carrier ampholytes through the gel or bycovalently incorporating a gradient of acidic and basic buffering groupswhen the gel strip is cast). The protein molecules migrate along the gelin response to an applied electric field until they reach a point in thegel where the gel pH matches the protein's isoelectric point (i.e., thepH at which the net charge on the protein is zero). Isoelectric focusingcan be used to discriminate between proteins having differences inisoelectric point as small as 0.01. See Stryer, Biochemistry, 4th. ed.,pp. 46-48, the entire contents of which are hereby incorporated byreference.

[0008] In order to increase resolution of the isoelectric focusing, itis desirable that the proteins be denatured prior to and duringseparation. Denaturation helps to provide a single protein configurationfor each protein, and to minimize interactions between protein moleculesor aggregation, as well as to expose internal ionizable amino acids.Denaturation, as well as solubilization of the protein, is typicallyachieved by placing the protein in a solution containing urea and/ordetergent prior to application to the gel.

[0009] In SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gelelectrophoresis), mixtures of proteins are separated according to thedifference in protein molecular weights. The protein is contacted withSDS, which is an anionic detergent. The detergent both denatures theprotein, and provides a large negative charge to the protein molecules,swamping the effect of any charge carrying groups on the protein itself,and providing a mechanism by which the protein will migrate in anelectric field. The protein mixture is typically combined with SDS orapplied to a gel containing SDS, and electrophoresed down the gel, sothat proteins having lower molecular weights travel farther.

[0010] Two-dimensional (or 2-D) electrophoresis is a widely used methodfor the analysis of complex protein mixtures extracted from cells,tissues, or other biological samples. The technique sorts proteins bycombining the IEF and SDS-PAGE techniques in two discrete steps. In oneof these steps, generally the first step, IEF is used to separate theproteins according to their differing isoelectric points. The other,generally second, step separates the proteins according to theirmolecular weight, using SDS-PAGE gel electrophoresis. The molecularweight separation is carried out across a dimension of the gel normal tothe first dimension of the gel (i.e., normal to the pH gradient).Typically, this is done by placing the strip obtained from IEF acrossthe top of a polyacrylamide gel containing SDS and applying an electricfield. The result is a two-dimensional “map” of spots of separatedproteins, each having a characteristic pI and molecular weight. With alarge enough gel, 2-D electrophoresis can be used to separate largenumbers of different proteins from a single sample. In addition toproviding information about the isoelectric points, and apparentmolecular weights of these proteins, the amount of protein present inthe sample may also be determined. 2D electrophoresis is also useful toanalyze cell differentiation, detect disease markers, monitor therapies,micropurify proteins, as well as in cancer research and drug discovery.

[0011] The gels used for isoelectric focusing and for 2-Delectrophoresis can be supplied in the form of prepared strips that arethen supported by a stripholder. Solution to rehydrate the strips and/orapply the sample thereto may be supplied to the stripholder, and thestrip inserted.

[0012] Ceramic materials, while desirable for use in electrophoresisequipment due to their high electrical breakdown strength, high thermalconductivity, chemical inertness, and low cost, can create problems insuch applications due to the somewhat hydrophilic nature of the ceramicsurfaces. In particular, when used to make stripholders of the typedescribed above, the urea-containing and/or detergent containing proteincarrying solutions tend to wick over the stripholder walls. The wickingsolutions carry protein sample with them, leading to loss of samplematerial and potentially inaccurate results of the isoelectric focusingand 2-D electrophoresis.

[0013] Similar problems occur with ceramic materials used formicroarrays of multiwell plates used in combinatorial chemistry.

[0014] Accordingly, there is a need in the art for methods of treatingceramic surfaces to lessen or avoid the wicking phenomenon responsiblefor sample loss and potentially inaccurate electrophoresis results, andfor ceramic surfaces so treated and for articles, in particular IEF andelectrophoresis sample holders, made therefrom.

SUMMARY OF THE INVENTION

[0015] The invention provides two methods for modification of ceramicsurfaces so as to reduce or avoid the wicking phenomenon associated withsample loss and potential inaccuracies in IEF or electrophoresis sampleholders.

[0016] In one method, the surface of the ceramic material that will comeinto contact with aqueous solutions is mechanically polished with anabrasive material until the wettability of the ceramic surface by theaqueous solution is decreased. This decrease is sufficient to lessen orprevent wicking. In a particular embodiment of this method, the ceramicsurface is the surface of a IEF or gel electrophoresis sample holder ora microarray plate for use in combinatorial chemistry.

[0017] In another method, the surface of the ceramic material ismodified by a silane heat-treatment method, whereby a silane iscontacted with the ceramic surface and heated for a sufficient time andat a sufficient temperature to decrease the wettability of the ceramicsurface (and, it is believed, the silane is covalently reacted with thehydroxyl moieties on the ceramic surface). In a particular embodiment ofthis method, the ceramic surface is the surface of a IEF or gelelectrophoresis sample holder or a multiwell microarray plate for use incombinatorial chemistry. Desirably, these sample holders have a ceramicsurface having a contact angle of greater than about 40° when in contactwith an aqueous solution of from about 6 M to about 9.8 M urea.

[0018] Both methods are believed to modify the surface characteristicsof the ceramic material in such as way as to decrease its ability toadhere to aqueous solutions, including aqueous solutions of biologicalmolecules, such as urea-containing or detergent-containingelectrophoresis solutions. This decreased adhesion (i.e., increasedhydrophobicity) between the ceramic material and the aqueous solutionsleads to decreased wettability, as measured by an increase in contactangle. The resulting ceramic material is suitable for use in articlesrequiring decreased wettability, and in particular,, for gel or gelstrip holders used in IEF or 2-D electrophoresis and microarrays ormicrowell plates of the type used in combinatorial chemistry. When usedin these applications, the ceramic material prepared by the inventionlessens or avoids the loss of sample material that has resulted fromwicking of sample solutions out of the ceramic container. This avoidanceof sample material loss increases the accuracy and reliability of theIEF, SDS-PAGE, combinatorial, or other analytical procedures carried outon the sample.

DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS OF THE INVENTION

[0019] As described above, one embodiment of the invention is directedto a method for the mechanical polishing of the ceramic surface is onemethod disclosed for the reduction of wetting by the solution(s).Polishing can be achieved through several standard methods; thesemethods include, but are not limited to: lapping, tumbling, vibratorymilling. These procedures can be carried out with a slurry containingthe abrasive or abrasives. Contact with a rotating polishing wheelcontaining the abrasive may also be used. The abrasives used may be ofany form and of any particle size that will provide the desired results.Diamond particles have been found to be suitable, in particular diamondparticles having a particle size ranging from about 3 microns to about 9microns, and having an average particle size of around 6 microns.Silicon carbide particles can also be used, in particular those having asimilar range of particle sizes and a similar average particle size.

[0020] Polishing is generally completed when the ceramic surface hasbeen rendered visibly reflective. More particularly, the surface finishcan be checked after polishing to determine if sufficient polishing(i.e., a sufficient polishing time) has occurred. Polishing cangenerally be discontinued when the surface finish ranges from about 8 toabout 15 microinches (about 2*10⁻⁵ cm to about 4*10⁻⁵ cm). Typically,this will require a polishing time of about 10 sec. to about 20 sec. persquare centimeter of surface.

[0021] Following polishing, the ceramic surface is cleaned to remove anyremaining abrasive particles and/or abraded pieces of ceramic material.For example, the surface can be wiped, e.g., with a paper towel,contacted with a water solution of dishwashing detergent (e.g., Dawn),spray rinsed with warm tap water. This can be repeated several times asneeded. A final rinse with deionized water and drying with, e.g., apaper towel can then be conducted.

[0022] The mechanical polishing process of the invention can increasethe contact angle between ceramic materials, such as alumina, andsolutions, such as aqueous urea solutions, from about 15° to about 20°,prior to treatment, to above about 40° after treatment.

[0023] As also described above, the wettability of ceramic surfaces canbe modified by a silane heat treatment according to the invention, andthis modification lessens the ability of aqueous solutions, such asprotein solutions containing denaturing agents, to spread or wick overthe ceramic surface. While not wishing to be bound by any theory, it isbelieve that this decreased wetting results at least in part becausereaction of the silane with isolated hydroxyl moieties on the ceramicsurface in effect removes the hydrophilic nature of these moieties withhydrophobic alkyl-containing silane groups. These isolated hydroxylmoieties can be thought of as chemically bonded water that is not easilyremoved from the surface of the ceramic material. Normally, they areremoved only with great difficulty, requiring very high temperatureexposure (e.g., exposure to temperatures of around 800° C. to around1200° C.). Under this theory, the method for modifying a ceramicsurface, comprises;

[0024] (a) contacting the surface with an alkyl-containing silane; and

[0025] (b) heating the surface and the alkyl-containing silane underconditions sufficient to react at least a portion of the hydroxyl groupson ceramic surface with the alkyl-containing silane.

[0026] The reaction is believed to proceed as shown in equation (1):

Y—OH+Si(X)_(n)(alkyl)_(4-n)

Y—O—Si(X)_(n-1)(alkyl)_(n-4)+HX   (1)

[0027] where n is an integer between 1 and 3, Y is an inorganic speciescapable of binding to hydroxyl moieties at the ceramic surface, and X ishalogen or other suitable leaving group. The reaction of TMCS with analumina-containing ceramic material is provided below in equation (2) asa more specific example (it will be understood by those skilled in theart that both Y and Al are bonded to other atoms in the ceramicmaterial, which other atoms are not shown in the interest ofconvenience:

Al—OH+Si(Cl)(CH₃)₃

Al—O—Si(CH₃)₃+HCl.   (2)

[0028] The silane heat treatment procedure can, of course, be combinedwith other techniques for removing physically bonded water and forremoving chemically bonded water in the form of adjacent hydroxylmoieties (both of which can be accomplished by heating, as described inmore detail, below).

[0029] The ceramic surface to be treated may be of any ceramic materialthat may come into contact with aqueous solutions under conditions wherewettability must be lessened or minimized. Often, the ceramic surfacewill be alumina or an alumina-containing material. The aqueous solutionsmay be solutions of detergent and/or urea, e.g., aqueous solutionscontaining about 6 M to about 9.8 M urea.

[0030] The ceramic surface is contacted with the alkyl-containing silanecapable of reacting with the surface hydroxyls. This silane may be amethyl-containing silane, more particularly a methyl-containing silanehaving a halo-silyl bond. Trialkylhalosilanes, in particulartrimethylhalosilanes such as trimethylchlorosilane (TMCS),trihaloalkylsilanes, in particular trihalomethylsilanes, such astrichloromethylsilane, and dialkyldihalosilanes, in particulardimethyldihalosilanes, such as dimethyldichlorosilane are examples ofsuitable silanes. The silane may be applied as a solution in a solvent(e.g., ethanol) in a concentration of between about 5 wt % and about 100wt %, or may be applied neat. The length of Contacting time may varywith the ceramic material, but is long enough to sufficiently reactavailable hydroxyl moieties and provide the requisite hydrophobicity (orat least decrease in hydrophilicity). Typical contact times range fromabout 1 min. to about 60 min, more particularly around 10 min. Thesilane used in the contacting step may be in the form of either a liquidor a vapor.

[0031] After the requisite contact time has elapsed, the coated ceramicmaterial is heated in order to remove residual unreacted silane and tostabilize the reaction surface. Heating can be at any temperaturebetween about room temperature and about 800° C., but typically isconducted at a temperature of about 200° C. to about 500° C., moreparticularly, about 200° C. to about 400° C. Heating is carried out fora period of time sufficient to remove residual unreacted silane andstabilize the surface, typically ranging from about 10 min. to about 90min., more particularly about 30 min. The heating can be carried out inan inert environment (e.g., in an Ar or N₂ atmosphere, or in a vacuum),in a reducing atmosphere (e.g., in the presence of H₂ or CO), or in anoxidizing atmosphere (e.g., in the presence of air, O₂, CO₂, etc.). Whenan inert atmosphere is used, the maximum heating temperature istypically the decomposition temperature of the Si—CH₃ group (atemperature of approximately 800° C. will produce SiC). When anoxidizing atmosphere is used, the maximum heating temperature istypically the oxidizing temperature of the Si—O—CH₃ group, which istypically about 400° C.

[0032] As an example of a suitable contacting/heating arrangement, thesilane heat treatment can be performed in a glove box under a nitrogenatmosphere, which reduces reaction of the silane with moisture containedin the air. The presence of organic materials, e.g., Tygon tubing inprocess equipment, is desirably avoided during the contacting andsubsequent heating step, since most organic materials will also reactwith the silane, potentially reducing the effectiveness of thetreatment.

[0033] The silane heat treatment of the invention is capable ofincreasing the contact angle between ceramic materials, such as alumina,and solutions, such as aqueous solutions of urea from about 15° to about20°, prior to treatment, to above about 40°, more particularly aboveabout 80° to about 90°, or even higher, after treatment.

[0034] As described above, the silane heat treatment can be combinedwith other methods for removing physically bonded water and more easilyremovable chemically bonded water, and these methods are typicallyperformed prior to the silane heat treatment step. For example,physically bonded water (e.g., water bonded to surface hydroxyl groupsor to other surface species by hydrogen bonding) can be removed byheating the ceramic material to a temperature ranging from around 70° C.to around 150° C., more particularly, around 110° C. to around 120° C.,for periods of time ranging from about 10 min. to about 120 min., moreparticularly, about 30 min. to about 60 min. Other suitable methods forremoving physically bonded water include vacuum treatment (i.e., placingthe ceramic material in a pressure sufficiently below atmospheric for asufficient time that the physically bonded water is released), andsolvent washing (e.g., contacting the ceramic surface with a watermiscible solvent such as acetone). Chemically bonded water tied up inadjacent surface hydroxyl groups can be removed by heating the ceramicmaterial to a temperature of about 500 ° C.

[0035] Both mechanical polishing and silane heat treatment may, ifdesired, be carried out on the same material.

EXAMPLES

[0036] The invention is further described below with respect tononlimiting examples thereof, which are not intended to restrict thescope of the invention in any way.

Example 1 Mechanical Surface Polishing Method

[0037] The internal walls of an alumina electrophoresis stripholder werepolished using a rotating polishing wheel and a slurry containingdiamond particles approximately 6 microns in average diameter, andhaving a particle size distribution of: 5% 10% 50% 90% 95% >7.8 μm >7.2μm >5.8 μm >4.8 μm >4.5 μm

[0038] Prior to polishing, the surfaces were visibly dull, and anaqueous solution of urea (a typical protein carrying solution) wasobserved to readily wick up the sides of the strip holder. Polishing wascarried out for 10-20 sec. per cm² of surface.

[0039] After polishing, the ceramic surface was cleaned by wiping offexcess polishing material with a paper towel, repeatedly (6 times)dipping and shaking the material in a 20 ml/L solution of DAWNdishwashing detergent at room temperature for about 5 seconds and sprayrinsing, finally rinsed with deionized water at room temperature, andwiping dry with paper towel.

[0040] The surface was visibly reflective (shiny) and urea was observedto remain in the bottom of the stripholder and not wick up the polishedstripholder walls. Contact angle for a urea solution of the typetypically used for electrophoresis of proteins increased from 15-20°before polishing to 40-50° after polishing. Polishing of the ceramicthus increased the urea contact angle and minimized urea wetting.

Example 2 Silane Heat Treatment

[0041] An alumina electrophoresis stripholder was heat treated at 110°C. for 30 minutes to remove physically attached water. The alumina wasthen dipped into a trimethylcholorosilane (TMCS) solution for 15minutes. After the treatment, the sample was heated to a temperature(400° C.) in an oven to complete the reaction and remove the residualsilane. After the treatment, the contact angle between urea and thetreated alumina surface was measured using an optical comparator by OGP,Inc. Values measured after the silane treatment were 80-90°, the contactangle for non-treated samples was 15-20°. This large increase of contactangle demonstrates that the solution wetting was drastically reduced bythe silane treatment. Following the treatment, tests were also done toinsure the durability of the modified surface. Two cleaning tests wereperformed:

[0042] 1. 8 hours in an ultrasonic bath with 20cc/liter Dawn detergentat 85° C.;

[0043] 2. 300 scrubs with a medium nylon brush (medium pressure toinsure bristle ends made right angle contact with surface);

[0044] In both cases, the surface appeared to be durable and functionedthe same before and after the cleaning tests.

[0045] The invention having been thus described by reference to variousspecific embodiments, it will be apparent that other variations andmodifications are possible that do not depart from the spirit of theinvention, and such are intended to be encompassed within the scope ofthe appended claims or equivalents thereto.

What is claimed is:
 1. A method for modifying a ceramic surface,comprising polishing the surface with an abrasive under conditionssufficient to decrease the wettability of the ceramic surface by aqueoussolutions.
 2. The method according to claim 1, wherein the abrasivecomprises a slurry.
 3. The method according to claim 1, wherein theabrasive comprises particles having a particle size ranging from about 3microns to about 9 microns.
 4. The method according to claim 3, whereinthe abrasive comprises particles having an average particle size ofabout 6 microns.
 5. The method according to claim 1, wherein theabrasive comprises particles having a particle size distribution: 5% 10%50% 90% 95% >7.8 μm >7.2 μm >5.8 μm >4.8 μm >4.5 μm


6. The method according to claim 2, wherein the abrasive comprisesdiamond particles.
 7. The method according to claim 2, wherein theabrasive comprises silicon carbide particles.
 8. The method according toclaim 2, wherein the surface is polished by lapping, tumbling, vibratorymilling, or by contact with a rotating polishing wheel.
 9. The methodaccording to claim 1, wherein the surface is polished for approximately10-20 seconds/cm² of ceramic surface.
 10. The method according to claim1, wherein the surface is polished until it becomes visibly reflective.11. The method according to claim 1, wherein the surface is polisheduntil it has a surface finish of about 8 to about 15 microinches afterpolishing.
 12. The method according to claim 1, wherein the ceramicsurface exhibits a contact angle with the aqueous solution thatincreases from about 15-20° before polishing to about 40-50° afterpolishing.
 13. A method for modifying a ceramic surface, comprisingcontacting the ceramic surface with a silane and heating for asufficient time at a sufficient temperature to decrease the wettabilityof the ceramic surface by aqueous solutions.
 14. A method for modifyinga ceramic surface, comprising, (a) contacting the surface with analkyl-containing silane; and (b) heating the surface and thealkyl-containing silane under conditions sufficient to react at least aportion of the hydroxyl groups on ceramic surface with thealkyl-containing silane.
 15. The method according to claim 13, whereinthe silane is a methyl silane.
 16. The method according to claim 13,wherein the silane is a halotrialkylsilane.
 17. The method according toclaim 16, wherein the halotrialkylsilane is trimethylchlorosilane. 18.The method according to claim 13, wherein the silane is adihalodialklysilane.
 19. The method according to claim 18, wherein thedihalodialklysilane is dichlorodimethylsilane.
 20. The method accordingto claim 13, wherein the silane is a trihalomethylsilane.
 21. The methodaccording to claim 20, wherein the trihalomethylsilane istrichloromethylsilane.
 22. The method according to claim 13, furthercomprising, removing unreacted residual silane from the surface.
 23. Themethod according to claim 22, wherein the removal is accomplished byheating.
 24. The method according to claim 13, further comprisingremoving at least a portion of physically attached water on the ceramicsurface prior to contacting.
 25. The method according to claim 24,wherein said physically attached water is removed by heating thesurface.
 26. The method according to claim 25, wherein the surface isheated to a temperature between about 70° C. and about 150° C.
 27. Themethod according to claim 26, wherein the surface is heated to atemperature between about 110° C. and about 120° C.
 28. The methodaccording to claim 25, wherein the surface is heated for a time betweenabout 10 min. and about 120 min.
 29. The method according to claim 28,wherein the surface is heated for a time between about 30 min. and about60 min.
 30. The method according to claim 24, wherein said physicallyattached water is removed by subjecting the surface to vacuum.
 31. Themethod according to claim 24, wherein said physically attached water isremoved by washing the surface with a solvent.
 32. The method accordingto claim 31, wherein the solvent is water miscible.
 33. The methodaccording to claim 32, wherein the water miscible solvent is acetone.34. The method according to claim 13, wherein the contacting comprisesexposing the ceramic surface to a silane that is either a neat liquid orin the form of a solution or vapor for a time ranging between about 1min. and about 60 min.
 35. The method according to claim 34, wherein thesilane is in the form of a neat liquid.
 36. The method according toclaim 34, wherein the silane is in the form of an ethanol solutionhaving a concentration of silane between about 5 wt % and about 100 wt%.
 37. The method according to claim 13, wherein the heating comprisesexposing the ceramic surface and silane to a temperature between aboutroom temperature and about 800° C. for a time between about 10 min. andabout 90 min.
 38. The method according to claim 37, wherein the heatingcomprises exposing the ceramic surface and silane to a temperaturebetween about 200° C. and about 500° C.
 39. The method according toclaim 37, wherein the heating comprises exposing the ceramic surface andsilane to said temperature for a time between about 10 min. and about 30min.
 40. The method according to claim 13, wherein the ceramic surfaceexhibits a contact angle with an aqueous solution that increases fromabout 15-20 degrees prior to modifying to about 80-90 degrees aftermodifying.
 41. A ceramic material comprising a surface that has beentreated by polishing the surface with an abrasive under conditionssufficient to decrease the wettability of the ceramic surface by aqueoussolutions.
 42. The ceramic material according to claim 41, wherein theceramic surface comprises alumina.
 43. A ceramic article made from theceramic material of claim
 41. 44. The ceramic article of claim 43, whichis selected from the group consisting of an IEF gel strip holder, a gelsupport, and a microarray plate.
 45. A ceramic material comprising asurface that has been treated by contacting the ceramic surface with asilane and heating for a sufficient time at a sufficient temperature todecrease the wettability of the ceramic surface by aqueous solutions.46. The ceramic material according to claim 45, wherein the ceramicsurface comprises alumina.
 47. A ceramic article made from the ceramicmaterial of claim
 45. 48. The ceramic article of claim 47, which isselected from the group consisting of an IEF gel strip holder, a gelsupport, and a microarray plate.
 49. A sample holder for chemicalanalysis, comprising a ceramic surface having a contact angle of greaterthan about 40 with an aqueous solution comprising about 6 to about 9.8 Murea.
 50. The sample holder of claim 49, which is adapted to hold a gelstrip for isoelectric focusing.
 51. The sample holder of claim 49, whichis adapted to hold an electrophoresis gel.
 52. The sample holder ofclaim 49, which is a multiwell microarray plate.